The importance of tubulointerstitial injury in the early phase of primary glomerular disease

Hruby Z, Smolska D, Filipowski H, Rabczyn'ski J, Cies'lar E, Kopec' W, Dulawa J. (University of Medicine, Wroczlaw; and Silesian Academy of Medicine, Katowice; Poland). The importance of tubulointerstitial injury in the early phase of primary glomerular disease. J Intern Med 1998; 243: 215–22. Objectives As tubulointerstitial damage is regarded secondary to glomerular injury in primary glomerulopathies, we assessed lesions to renal tubulointerstitium in recently diagnosed primary glomerular diseases and evaluated their impact on progression of the disease during the first 2 years after diagnosis. Design A nonrandomized prospective study assessing tubulointerstitial morphometry at diagnosis, markers of tubular function within the next 6 months and progression of the disease (creatinine clearance) during 24 months' follow‐up. Setting Single tertiary referral centre. Subjects Forty‐six patients with primary glomerular disease, the diagnostic oligobiopsy performed within 2 months of the onset of clinical symptoms. Interventions All patients were subjected to anti‐inflammatory/immunosuppressive treatment. Main outcome measures Alterations in results of tubulointerstitial morphometry and tubular function tests, correlations between these variables and parameters of nephrosis/renal function, selection of the most accurate predictor of disease progression within 24 months after diagnostic biopsy. Results Function of proximal tubules, markedly deteriorated at the time of diagnosis, significantly improved 6 months later (urinary β2‐microglobulin: P < 0.0025), along with reduction in proteinuria (P < 0.00125). No appreciable alterations in function of distal tubules were noted. Morphometric indices revealing interstitial expansion and tubular atrophy significantly correlated with creatinine clearance at 6 months (P= 0.032) and were the best predictors of deteriorating renal function at 24 months. Excretion of β2‐microglobulin at the time of diagnosis was the best marker for impairment of glomerular filtration 6 months later. Conclusions Significant damage to cortical tubulointerstitium occurs concurrently with glomerular injury in primary glomerulopathies and may predict the clinical course of the disease already in its initial phase.